Revising HIV's History

MINNEAPOLIS, MINNESOTA--The human immunodeficiency virus (HIV-1) responsible for most of the AIDS cases in the world infected people approximately 100 years ago, more than 20 years earlier than previously believed, according to findings presented here this week at the Evolution 2008 meeting. Its lesser known cousin, HIV-2, jumped into humans decades later, from a monkey species that carried the virus for just a couple of hundred years, not the millions of years researchers had assumed, according to other research presented at the meeting.

Researchers are trying to pin down the origins of both HIVs to understand how often new human viruses emerge. Both arose from simian immunodeficiency viruses (SIVs) of other primates.

The first clues that researchers were on the wrong track about the SIV that led to HIV-2 came last year. Researchers had assumed that because most monkey species infected with SIV don't get sick, the virus has been coevolving with the primates for millions of years, allowing the host and pathogen to peaceably coexist. If that were the case, the branching of the monkey family tree should match the branching of the SIV tree. But last year, University of Arizona, Tucson, graduate student Joel Wertheim, his adviser, Michael Worobey, and colleagues found that not to be the case for the African green monkey and its SIV. "The work suggested that the virus was not millions of years old," Wertheim said at the meeting.

To better pin down the origin of SIVs, Wertheim then collected samples of the virus from sooty mangabeys in Africa and in U.S. primate centers. (These samples were far more plentiful than virus from African green monkeys.) He compared the genetic sequences in those SIV samples with sequences from the few African green monkey SIV samples he had, as well as to sequences of human HIV-2 and macaque SIV.

Wertheim used a sophisticated computer program to build a family tree based on the degree of differences among the sequences. The analysis also determined when the various strains--branches on this tree--appeared. The sooty mangabey caught its first SIV in 1808, and it jumped into humans 125 years later to become HIV-2, he reported at the meeting.

In the second study, another of Worobey's graduate students, Marlea Gemmel, analyzed HIV-1 genetic material obtained from lymph tissue collected in 1960 from the University of Kinshasa pathology department in the Democratic Republic of the Congo--only the second HIV sequence predating 1976 deciphered to date. Thus far, she has sequenced about 1000 DNA bases, which she has compared with the previously reported sequence of HIV-1 extracted from a frozen blood sample from 1959. Since it entered into humans, HIV-1 has been evolving into different substrains--but the 1960 and 1959 sequences were much more divergent than expected, Gemmel reported at the meeting. "It reflects a long past of diversification before 1960," she said.

By comparing the two sequences with more recent ones, Gemmel was able to show that HIV-1 first entered humans about 1908, not 1931, as earlier analyses with just the 1959 sample found. Her analysis also indicates that the virus existed in low levels in humans until the middle of the 20th century. "That matches the rise of population centers," Gemmel explained, suggesting that urbanization around that time paved the way for the AIDS epidemic.

Experts are impressed by both findings. The Worobey group is "applying state-of-the-art tools and controlling for a lot of important issues" in shedding light on the origins of the AIDS epidemic, says John Logsdon Jr., an evolutionary biologist at the University of Iowa, Iowa City. These studies are also helping us understand how HIV works, says David Hillis, an evolutionary biologist at the University of Texas, Austin. For example, AIDS experts have assumed that the disease is so severe in humans--yet less so in most monkeys--because humans have not had the time to evolve the proper defenses against the virus that many other primates have. "But the origins are around the same order of magnitude," and still the monkeys don't get sick, says Hillis. "It points out that there are other directions we need to go to understand [virulence]."